High-grade nucleoside transport inhibition stimulates ventilation in humans.

In 6 healthy male volunteers a placebo-controlled, double-blind, randomized, crossover trial was done to assess the effect of 1, 2, 4, and 6 mg of draflazine, a specific nucleoside transport inhibitor, on ventilation. Draflazine increased thoracic excursions dose-dependently by maximally (median with 95% confidence interval) 114.0% (38.3-184.8%) without affecting breathing rate. Ex vivo adenosine transport was inhibited by 0% (0-1%) after placebo, and 70% (59-74%), 81% (76-85%), 90% (86-93%), and 93% (90-96%) after the 4 increasing draflazine dosages, respectively (P < .05 for each draflazine dosage versus placebo). These results indicate that endogenously released adenosine may play a role in the regulation of ventilation.